The preclinical profile of lurasidone: clinical relevance for the treatment of schizophrenia

Abstract

Introduction: Lurasidone is a novel antipsychotic drug approved for the treatment of schizophrenia in adults. It is formulated into tablets, administered orally once/day (dose range 40 – 160 mg/day) does not require titration, but needs to be given with food to maximize its plasma exposure.

Areas covered: This review focuses on the preclinical discovery of lurasidone. Furthermore, the article provides analysis on the pharmacological, behavioral and molecular mechanisms of lurasidone and their contribution to its therapeutic advantages. The article is based on the literature reported in published preclinical and clinical studies, product labels, poster presentations and press releases.

Expert opinion: Lurasidone demonstrated high affinity for serotonin 5-HT_1A, 5-HT_2A, 5-HT₇, dopamine D₂ and adrenergic α_2C receptors followed by α₁ and α_2A receptors. The drug was active in animal models predictive of antipsychotic and antidepressant activities. In addition, it demonstrated procognitive effects, as it was effective in several animal models that assessed memory, cognition and executive functions in rats and in primates. At a cellular level, lurasidone promotes neuronal plasticity, can modulate epigenetic mechanisms controlling gene transcription, and increases the expression of the neurotrophic factor BDNF in cortical and limbic brain regions. Lurasidone's mechanisms of action might contribute to its unique psychopharmacological properties in the improved treatment of schizophrenia, and perhaps other psychiatric disorders.

Keywords::

• animal models
• brain-derived neurotrophic factor
• cognition
• depression
• epigenetics
• receptor pharmacology
• schizophrenia

Notes

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